The program is designed to characterize the functions of respiratory epithelia in health and disease. The specific goals include: (1) a description of pulmonary surface liquid metabolism that integrates the functions of alveolar and of small and large airways surfaces in regulating the ionic, mucin and protein composition and volume of the surface liquid; (2) an elucidation of the mechanisms that control the rate of epithelial activities, focussing upon regulation via cytosolic Ca++ activity, arachidonic acid metabolites, cAMP mediated mechanisms, and energy metabolism; (3) changes in epithelial functions consequent to maturation; and (4) abnormalities in epithelial function in disease, e.g., cystic fibrosis (CF). Where possible the research proposed will focus on human respiratory epithelia and will employ physiologic, biochemical, pharmacologic, ultrastructural, cell biological and clinical approaches. The component projects will: (1) use microelectrode, optical, and biochemical techniques to describe alveolar ion transport activities in adult and fetal animals, and describe the mechanisms that control the functional state and number of ion paths; (2) use cell biological and biochemical approaches to evaluate rates and control of mucin synthesis and secretion in different elements of human airways (gland vs. goblet cell) from normal and diseased subjects; (3) use physiologic and ultrastructural techniques to investigate the modes of protein-translocation across airway epithelia; (4) investigate the control of ion transport in human airways (both large and small airway) focussing on arachidonic acid and cAMP derived products, integrating these studies with others designed to refine tissue culture techniques for the study of human respiratory epithelia; (5) using clinical techniques, investigate in vivo the coordination between secretory elements of nasal mucosa, glands and superficial epithelium, and their contributions to disease, e.g., C.F. Together, these projects will develop a framework for characterizing the functions and control of respiratory epithelial activities which may permit more specific approaches for the diagnosis, treatment and prevention of diseases, e.g., asthma, infection, neonatal distress syndromes, and CF that reflect a dysfunction of this tissue.